The Familial Lentiginosis Syndromes are Emerging from the Obscurity Imposed by Rarity: New Genes and Genetic Loci for Multiple Tumors and Developmental Defects*

Lentigines (similar but not identical to “ephelides” or “freckles”) are common skin lesions, which, in a small number of patients, can be of great interest to endocrinologists and other nondermatological specialists. In these cases, lentigines constitute part of genetic syndromes that are associated with inherited forms of neoplasias or other pathologic processes of the cardiovascular, endocrine, and gastrointestinal systems. The familial lentiginoses, as these syndromes are collectively known, include the Leopard and Peutz-Jeughers syndromes, Carney complex, and the newly described “syndrome of arterial dissections with lentiginosis”. Additional disorders, like Cowden's disease, Bannayan-Ruvalcaba-Riley syndrome and others, have phenotypes that overlap with the lentiginoses. Macronodular adrenocortical hyperplasia is a special case in the cohort of diseases reported here, because it is not associated with any skin lesions; however, the bilateral nature of adrenocortical defects and the new molecular insights into its pathophysiology make it a disorder particularly interesting to the researchers that investigate primary pigmented adrenocortical disease (PPNAD), the adrenal pathology seen in Carney complex. In the majority of the reported kindreds with lentiginosis and related syndromes, the lesions are inherited in an autosornal dominant manner. The genetic loci and specific genes for these syndromes are now under intense investigation. These genes appear not only to participate in the pleiotropy of human pigmentation, but also to be involved in the function, growth and proliferation of other neural crest and mesenchymal cells. The abstracts that follow describe the most recent advances in the field of familial lentiginosis as well as provide us with some insight from the pioneers in the field: Dr. McCusick (Peutz-Jeghers syndrome), Dr. Gorlin (LEOPARD syndrome), Dr. Carney (Carney complex). This represents a unique blend of clinical and basic research, medical history and molecular biology, made possible by a generous grant from the Office of Rare Diseases (ORD), Office of the Director (OD), National Institutes of Health (NIH), which funded the “1^st International Meeting on Carney complex and related disorders” held at the NIH on May 1^st, 1998. The abstracts are listed in the order they were presented at the meeting.

Key words

Lentigines - Peutz-Jeghers Syndrome - LEOPARD Syndrome - Myxomas - Cowden Disease - Carney Complex - Adrenal Gland